crossing96/oncoscreening huggingface dataset:
Association Between Body Mass Index and Outcomes in Patients With Urothelial Carcinoma Treated With Pembrolizumab.	BACKGROUND/AIM: We aimed to clarify the association between body mass index (BMI) and clinical outcomes of pembrolizumab treatment for advanced urothelial cancer (UC). PATIENTS AND METHODS: We retrospectively reviewed the records of patients with advanced UC who received pembrolizumab after chemotherapy between March 2018 and December 2021. Patients were divided according to BMI into the non-overweight group (BMI <25 kg/m(2)) and the overweight group (BMI ≥25 kg/m(2)). We compared the two groups' tumour response, survival rates, and incidence of immune-related adverse events (irAEs) and investigated the factors predicting survival. RESULTS: Of 84 eligible patients, 63 (75%) and 21 (25%) were in the non-overweight and overweight groups, respectively. Although the objective response rate was higher in the overweight group (55%) than that in the non-overweight group (29%), the difference was not significant. Progression-free survival (PFS) was significantly longer in the overweight group (median 15.2 months) than that in the non-overweight group (median 4.8 months; p=0.01). Overall survival was also longer in the overweight group (median 36.1 months) compared to that in the non-overweight group (13.4 months), but the difference was not significant (p=0.11). Multivariable analysis showed that overweight was significantly associated with favourable PFS. Any and severe (grade 3) irAEs were observed in 15 (24%) and 5 (7.9%) patients in the non-overweight group, respectively, and in 8 (38%) and 2 (9.5%) patients in the overweight group, respectively, but the differences were not significant. CONCLUSION: BMI was associated with oncological outcomes in patients with advanced UC who received pembrolizumab but not with the development of irAEs.	bladder
Extramammary paget disease of the penoscrotal region.	Extramammary Paget disease is an uncommon slow growing intraepithelial malignant neoplasm. It can be classified into primary and secondary subtypes, with secondary subtype associated with underlying malignancy. Extramammary Paget disease of the penoscrotal region is extremely rare with very limited literature available describing its clinicopathologic characteristics. We present 6 cases of penoscrotal EMPD diagnosed at our academic medical center over a 20 year period. These included 5 cases of scrotal EMPD and 1 case of penile EMPD. The mean age at diagnosis was 68.6 yrs. (Range 61-78 years), One case of scrotal EMPD had history of renal cell carcinoma and prostatic adenocarcinoma, while one other case presented as recurrent EMPD with initial disease in the left groin. EMPD in the glans penis was associated with a history of urothelial carcinoma in the ureter with pagetoid spread. 3 cases had no progression of the disease till recent follow up, 2 were lost to follow up while 1 case rapidly deteriorated resulting in death. This case had bone metastatic and associated peritoneal carcinomatosis. Thus, Extramammary Paget disease of the penoscrotal area is extremely rare, can be primary or associated with visceral malignancies and usually tends to present at an older age. Peritoneal spread and distant metastasis are associated with rapid progression of the disease.	bladder
Abietic acid induces ferroptosis via the activation of the HO-1 pathway in bladder cancer cells.	BACKGROUND: Bladder cancer (BC) is a common urological malignancy that still lacks effective treatments. Abietic acid (AA) is an abietane diterpene that possesses various biological activities, including antitumor activity. This study aimed at evaluating the effects of AA on BC cells. MATERIALS AND METHODS: The 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay was used to assess the effects of AA on the viability of BC cells. Annexin-V and FITC staining was used to assess cellular death. The type of cell death was determined by the administration of various specific cell death inhibitors. Commercial kits were used to measure the levels of reactive oxygen species (ROS), intracellular iron, malondialdehyde (MDA), and glutathione (GSH). Real-time polymerase chain reaction (RT-PCR) and western blot analysis were used to assay mRNA and protein levels, respectively. The role of glutathione peroxidase 4 (GPX4) in the antitumor effects of AA was evaluated using the forced expression of GPX4 in BC cells. The impact of HO-1 on the antitumor effects of AA was examined by gene silencing and pharmacological inhibition of the protein. Finally, the antitumor effects of AA were evaluated in xenograft models. RESULTS: AA selectively inhibited the viability of BC cells but not normal cells. AA-induced ferroptosis in BC cells was evidenced by the upregulation of ROS, intracellular iron, and MDA. AA treatment led to the downregulation of GPX4 and the upregulation of HO-1 in BC cells. Forced expression of GPX4 or inhibition of HO-1 resulted in decreased ferroptosis triggered by AA in BC cells. AA also showed synergistic effects with various chemotherapeutic agents against BC and inhibited the growth of BC cells in vivo. CONCLUSION: This study revealed AA-induced ferroptosis in BC cells both in vitro and in vivo. AA might be applied as a promising agent for the treatment of BC.	bladder
Atomic force microscopy-based assessment of multimechanical cellular properties for classification of graded bladder cancer cells and cancer early diagnosis using machine learning analysis.	Cellular mechanical properties (CMPs) have been frequently reported as biomarkers for cell cancerization to assist objective cytology, compared to the current subjective method dependent on cytomorphology. However, single or dual CMPs cannot always successfully distinguish every kind of malignant cell from its benign counterpart. In this work, we extract 4 CMPs of four different graded bladder cancer (BC) cell lines by AFM (atomic force microscopy)-based nanoindentation to generate a CMP database, which is used to train a cancerization-grade classifier by machine learning. The classifier is tested on 4 categories of BC cells at different cancer grades. The classification shows split-independent robustness and an accuracy of 91.25% with an AUC-ROC (ROC stands for receiver operating characteristic, and ROC curve is a graphical plot which illustrates the performance of a binary classifier system as its discrimination threshold is varied) value of 97.98%. Finally, we also compare our proposed method with traditional invasive diagnosis and noninvasive cancer diagnosis relying on cytomorphology, in terms of accuracy, sensitivity and specificity. Unlike former studies focusing on the discrimination between normal and cancerous cells, our study fulfills the classification of 4 graded cell lines at different cancerization stages, and thus provides a potential method for early detection of cancerization. STATEMENT OF SIGNIFICANCE: We measured four cellular mechanical properties (CMPs) of 4 graded bladder cancer (BC) cell lines using AFM (atomic force microscopy). We found that single or dual CMPs cannot fulfill the task of BC cell classification. Instead, we employ MLA (Machine Learning Algorithm)-based analysis whose inputs are BC CMPs. Compared with traditional cytomorphology-based prognoses, the non-invasive method proposed in this study has higher accuracy but with many fewer cellular properties as inputs. The proposed non-invasive prognosis is characterized with high sensitivity and specificity, and thus provides a potential tumor-grading means to identify cancer cells with different metastatic potential. Moreover, our study proposes an objective grading method based on quantitative characteristics desirable for avoiding misdiagnosis induced by ambiguous subjectivity.	bladder
A Modified and Practical Surgical Technique for Pure Transperitoneal Laparoscopic Radical Nephroureterectomy in a Single Position and Research Outcomes.	Purpose: To explore the surgical techniques and clinical value of pure transperitoneal laparoscopic nephroureterectomy (LNU) plus bladder cuff excision (BCE) conducted without changing the patient's position in the treatment of upper tract urothelial carcinoma (UTUC). Methods: From August 2018 to July 2021, we retrospectively reviewed 66 patients who underwent LNU + BCE in a single position. Then, their demographic characteristics, perioperative and pathological outcomes, and postoperative follow-up data were evaluated. Results: All 66 operations in this group were successfully completed without conversion to open surgery. The mean operative time was 125 ± 47 minutes, whereas the estimated blood loss was 10 (10, 15) mL. The median postoperative drainage time was 4 (3.8, 6.0) days, the time to catheter extraction after the operation was 4.5 (3.0, 6.0) days, and the median postoperative hospital stay was 6 (5, 7) days. Pathological results showed urothelial carcinoma in 65 cases, including 56 high-grade and 9 low-grade cases. Lymph node metastasis was found in 8 cases of high-grade urothelial carcinoma. All the surgical margins were negative. The median follow-up was 16.5 (11.0-25.6) months, and there was neither tumor recurrence nor distant metastasis. Conclusions: Pure transperitoneal LNU + BCE in a single position is a safe and effective minimally invasive technique for UTUC and is worthy of clinical application and promotion. It takes advantage of a programmed procedure, short operation time, less blood loss, less trauma, and quick recovery after the operation. However, multicenter randomized controlled studies with large samples are needed to further confirm these findings. Trial Registration: The study was registered at Cancer Hospital, Chinese Academy of Medical Sciences (No. 22/054-3255) and the registration date is August 2018.	bladder
Constructing and validating nomograms to predict risk and prognostic factors of distant metastasis in urothelial bladder cancer patients: a population-based retrospective study.	BACKGROUND: Urothelial carcinoma is the most common type of bladder cancer worldwide and it has a poor prognosis for patients with distant metastasis. Nomograms are frequently used in clinical research, but no research has evaluated the diagnostic and prognostic factors of distant metastasis in urothelial bladder cancer (UBC). METHODS: The Surveillance, Epidemiology, and End Results database was used to analyze all patients diagnosed with UBC between 2000 and 2017. Lasso regression was used to identify the potential risk predictive factors for distant metastasis in UBC. Univariate and multivariate Cox proportional hazard regression analyses were performed to determine independent prognostic factors for distant metastasis urothelial bladder cancer (DMUBC). Subsequently, two nomograms were constructed based on the above models. The receiver operating characteristic (ROC), and calibration curves were performed to evaluate the two nomograms. RESULTS: The study included 73,264 patients with UBC, with 2,129 (2.9%) having distant metastasis at the time of diagnosis. In the diagnostic model, tumor size, histologic type, and stage N and T were all important risk predictive factors for distant metastasis of UBC. In the prognostic model, age, tumor size, surgery, and chemotherapy were independent factors affecting the prognosis of DMUBC. DCA, ROC, calibration, and Kaplan-Meier (K-M) survival curves reveal that the two nomograms can effectively predict the diagnosis and prognosis of DMUBC. CONCLUSION: The developed nomograms are practical methods for predicting the occurrence risk and prognosis of distant metastasis urothelial bladder cancer patients, which may benefit the clinical decision-making process.	bladder
CD46 protects the bladder cancer cells from cetuximab-mediated cytotoxicity.	Epidermal growth factor receptor (EGFR) is an effective target for those patients with metastatic colorectal cancers that retain the wild-type RAS gene. However, its efficacy in many cancers, including bladder cancer, is unclear. Here, we studied the in vitro effects of cetuximab monoclonal antibodies (mAbs) targeting EGFR on the bladder cancer cells and role of CD46. Cetuximab was found to inhibit the growth of both colon and bladder cancer cell lines. Furthermore, cetuximab treatment inhibited AKT and ERK phosphorylation in the bladder cancer cells and reduced the expression of CD46 membrane-bound proteins. Restoration of CD46 expression protected the bladder cancer cells from cetuximab-mediated inhibition of AKT and ERK phosphorylation. We hypothesized that CD46 provides protection to the bladder cancer cells against mAb therapies. Bladder cancer cells were also susceptible to cetuximab-mediated immunologic anti-tumor effects. Further, cetuximab enhanced the cell killing by activating both antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) in bladder cancer cells. Restoration of CD46 expression protected the cells from both CDC and ADCC induced by cetuximab. Together, CD46 exhibited a cancer-protective effect against both direct (by involvement of PBMC or complement) and indirect cytotoxic activity by cetuximab in bladder cancer cells. Considering its clinical importance, CD46 could be an important link in the action mechanism of ADCC and CDC intercommunication and may be used for the development of novel therapeutic strategies.	bladder
Construction of Pyroptosis-Related Prognostic and Immune Infiltration Signature in Bladder Cancer.	Pyroptosis is a kind of programmed cell death related to inflammation, which is closely related to cancer. The goal of this study is to establish and verify pyroptosis-related gene signature to predict the prognosis of patients with bladder cancer (BLCA) and explore its relationship with immunity. Somatic mutation, copy number variation, correlation, and expression of 33 pyroptosis-related genes were evaluated based on The Cancer Genome Atlas (TCGA) database. BLCA cases were divided into two clusters by consistent clustering and found that pyroptosis-related genes were related to the overall survival (OS) of BLCA. The least absolute shrinkage and selection operator (LASSO) Cox regression was used to construct the signature (including 7 pyroptosis-realated genes). Survival analysis curve and receiver operating characteristic curve (ROC) showed that this signature could predict the prognosis of BLCA patients. Univariate and multivariate Cox regression analysis showed the independent prognostic value of this model. Immune infiltration analysis showed that the six types of immune cells have significantly different infiltrations. The effect of immunotherapy is better in the low-risk group. In summary, our effort indicated the potential role of pyroptosis-related genes in BLCA and provided new perspectives on the prognosis of BLCA and new ideas for immunotherapy.	bladder
BCG-activation of leukocytes is sufficient for the generation of donor-independent innate anti-tumor NK and γδ T-cells that can be further expanded in vitro.	Bacillus Calmette-Guérin (BCG), the nonpathogenic Mycobacterium bovis strain used as tuberculosis vaccine, has been successfully used as treatment for non-muscle invasive bladder cancer for decades, and suggested to potentiate cellular and humoral immune responses. However, the exact mechanism of action is not fully understood. We previously described that BCG mainly activated anti-tumor cytotoxic NK cells with upregulation of CD56 and a CD16(+) phenotype. Now, we show that stimulation of human peripheral blood mononuclear cells with iBCG, a preparation based on BCG-Moreau, expands oligoclonal γδ T-cells, with a cytotoxic phenotype, together with anti-tumor CD56(high) CD16(+) NK cells. We have used scRNA-seq, flow cytometry, and functional assays to characterize these BCG-activated γδ T-cells in detail. They had a high IFNγ secretion signature with expression of CD27(+) and formed conjugates with bladder cancer cells. BCG-activated γδ T-cells proliferated strongly in response to minimal doses of cytokines and had anti-tumor functions, although not fully based on degranulation. BCG was sufficient to stimulate proliferation of γδ T-cells when cultured with other PBMC; however, BCG alone did not stimulate expansion of purified γδ T-cells. The characterization of these non-donor restricted lymphocyte populations, which can be expanded in vitro, could provide a new approach to prepare cell-based immunotherapy tools.	bladder
Log Odds of Positive Lymph Nodes (LODDS) as an Independent Predictor of Overall Survival Following Radical Cystectomy in Urothelial Bladder Cancer: Time to Rethink Conventional Node Staging.	BACKGROUND: Radical cystectomy (RC) with lymph node dissection is the mainstay of treatment for patients with muscle-invasive bladder cancer (MIBC) and high risk non-MIBC. The American Joint Committee on Cancer's (AJCC) node staging and lymph node ratio (LNR) systems are used in estimating prognosis; however, they do not directly factor in negative dissected nodes. In this study, we evaluated the log odds of positive lymph nodes (LODDS), a novel measure of nodal involvement, as a predictor of survival. PATIENTS AND METHODS: Eighty-three patients who underwent RC were retrospectively included and their demographic and clinical data were collected. Kaplan-Meier curve and Cox regression were used for survival analyses. RESULTS: Median number of dissected lymph nodes was 13 (range 3-45). ROC curve analysis indicated -0.92 as the optimal LODDS cutoff. LODDS > -0.92 was associated with higher T stage, lymphovascular invasion, and significantly worse overall survival (OS) (mean OS 18.6 vs. 45.1 months, P-value < .001). Furthermore, we evaluated AJCC node staging, LNR, and LODDS in three separate multivariable Cox regression models. Among 3 different measures of nodal disease burden, only LODDS was an independent predictor of OS (HR 2.71, 95% CI 1.28-5.73, P = .009). CONCLUSIONS: Our results show that LODDS is an independent predictor of OS and outperforms AJCC node staging and LNR in forecasting prognosis among patients with urothelial bladder cancer who undergo RC.	bladder
The Misdiagnosis of Intravesical Ectopic Prostatic Tissue as a Tumor.	Ectopic prostatic tissue is rare, and it is usually only discovered by chance during imaging examinations or surgery. However, between 1967 and 2021, reports of ectopic prostatic tissue in the medical literature increased. It is rarely reported that ectopic prostatic tissue can be misdiagnosed as a nephrogenic adenoma (NA). This case study aimed to increase the awareness of ectopic prostatic tissue to improve its rates of diagnosis. This paper is focused on a 45-year-old male patient with a history of bladder lesions that were accidentally discovered through a health examination. A computed tomography scan revealed a homogeneous isoechoic mass in the posterior inferior wall of the bladder. At first, a transurethral cystoscopy revealed a smooth sessile mass covering the normal bladder mucosa, which was located in the middle of the interureteric ridge. The biopsy results suggested a possible intravesical NA. The mass was then completely resected under pneumovesicoscopy, and the pathological diagnosis was ectopic prostatic tissue. The clinical symptoms of ectopic prostatic tissue are similar to other bladder neoplasms, but there are too few characteristics available in imaging examinations to allow for an accurate diagnosis. Since ectopic prostatic tissue can present as a tumor in the bladder, urologists may easily misdiagnose the condition. Surgery is the basis of treatment for ectopic prostatic tissue, and it has a good prognosis.	bladder
Bladder paraganglioma treated with open partial cystectomy: a case report.	BACKGROUND: Bladder paraganglioma is a neuroendocrine tumor that accounts for less than 0.1% of all bladder tumors. Symptoms caused by catecholamine release such as hypertension, palpitation, syncope, and macroscopic hematuria are the most common findings. Treatment modalities include transurethral resection, and partial or total cystectomy. CASE PRESENTATION: A 38-year-old Turkish female patient was examined for hematuria that had been persisting for 6 months. Among the clinical findings, only hematuria was present. Absence of adrenergic symptoms such as hypertension, palpitations, and syncope at the first presentation made it difficult to consider bladder paraganglioma in the differential diagnosis. Therefore, cystoscopy and transurethral resection were performed with the thought of urothelial cancer. Findings such as hypertension and bradycardia that developed during diagnostic transurethral resection suggested that it might be bladder paraganglioma. After the radiological evaluation and endocrinological preparation, the patient underwent partial cystectomy. CONCLUSION: The rarity of cases having been reported in the literature leads to uncertainties in the management of bladder paraganglioma. Adrenergic symptoms developing during transurethral resection should suggest paraganglioma in the differential diagnosis. A multidisciplinary approach and medical treatment are mandatory to prevent life-threatening complications such as hypertensive crisis, vascular collapse, and multiple-organ system failure. We aimed to report the clinical presentation that includes only macroscopic hematuria mimicking urothelial cancer and to emphasize the multidisciplinary approach in the treatment.	bladder
Radical cystectomy and urinary diversion outcomes in patients with single vs. double renal unit: A 2:1 matched-pair analysis.	OBJECTIVE: To evaluate perioperative and functional outcomes of radical cystectomy (RC) and urinary diversion (UD) in patients with a single kidney (SK) vs. double kidneys (DK). METHODS: We reviewed records of patients who underwent RC for bladder cancer with a history of prior or concurrent nephrectomy at USC between 2004 and 2020. Patients with chronic kidney disease who were already on dialysis were excluded. UD, perioperative complications, and postoperative glomerular filtration rate (GFR) of the SK group were compared with a group of patients who underwent RC with DK using 2:1 matching with respect to age, sex, preop GFR, and tumor stage. RESULTS: We included 186 patients (SK = 62 and DK = 124). Half of the SK patients underwent continent UD. SK patients had a higher length of hospital stay compared to the DK group; however, 90-day complications, readmission, and mortality rates were similar. In patients with continent diversion, SK vs. DK showed similar 90-day complications (71% vs. 69%, P = 1.0). SK patients had significantly lower GFRs at discharge, 3-, and 12-month following RC compared to the DK group. Postoperative GFRs of the SK patients with continent vs. incontinent UD were statistically similar. On multivariable analysis, UD (i.e. continent vs. incontinent) was not associated with post-op GFR decline at discharge, 3- and 12-month following RC. CONCLUSIONS: Perioperative outcomes of radical cystectomy patients with single kidney are similar to double kidney patients, except for more GFR decline in single kidney cases. Continent urinary diversion in single kidney is as safe as double kidney patients.	bladder